The objectives of this work are to determine the orientation of two membrane bound proteins with respect to their membranes. In addition, changes in the position or motion of these proteins during function will be studied. The two proteins are acetylcholinesterase and the lac permease (beta-galactoside permease). The methods of spin labeling and EPR spectroscopy will be used in conjunction with fluorometry and radioisotopes. Active site directed irreversible inhibitors will also be employed.